title: Clinical trial safety and mortality analyses in patients receiving etanercept across approved indications.
abstract: OBJECTIVE
  Assessment of associations between etanercept treatment and rare adverse events has been limited by the size of clinical trial populations. The authors examined the collective safety of etanercept in clinical trials across approved indications.
  
  
  METHODS
  Forty-nine U.S. and non-U.S. trials of etanercept, involving up to 13,977 patients for approved indications, with final trial reports as of May 2006, were selected from the Amgen Inc. clinical trials database. Exposure-adjusted rates of serious infections, opportunistic infections, malignancies, and deaths were reported by trial, indication, and dosage.
  
  
  RESULTS
  Rates of serious infections were generally similar between etanercept and controls. Overall rates of opportunistic infections and tuberculosis were low. The standardized incidence ratio (SIR) (95% CI) for malignancy was 1.00 (0.83-1.19) for all etanercept patients across all indications. The SIR for lymphoma for patients with rheumatoid arthritis was 3.45 (1.83-5.89); all other indications reported SIRs similar to those observed in the general population. The SIRs for cutaneous squamous cell carcinoma in patients with psoriasis relative to the general population with high or low sun exposure were 2.09 (1.27-3.22) and 4.96 (3.03-7.66), respectively. SIRs were less than 1.0 for all other indications regardless of sun exposure. Rates of melanoma and basal cell carcinoma were not significantly different from those in the general population. There was no increase in mortality associated with etanercept use relative to control populations.
  
  
  CONCLUSIONS
  These data support the overall tolerability of etanercept across approved indications.
authors.affiliation: Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA. agottlieb@tufsmedicalcenter.org
authors.forename: Alice B
authors.initials: AB
authors.lastname: Gottlieb
authors.forename: Kenneth
authors.initials: K
authors.lastname: Gordon
authors.forename: Edward H
authors.initials: EH
authors.lastname: Giannini
authors.forename: Philip
authors.initials: P
authors.lastname: Mease
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Chon
authors.forename: Judy
authors.initials: J
authors.lastname: Maddox
authors.forename: Haoling H
authors.initials: HH
authors.lastname: Weng
authors.forename: Joseph
authors.initials: J
authors.lastname: Wajdula
authors.forename: Shao-Lee
authors.initials: SL
authors.lastname: Lin
authors.forename: Scott W
authors.initials: SW
authors.lastname: Baumgartner
mesh_terms: D001171:Arthritis, Juvenile / Q000188:drug therapy; D015535:Arthritis, Psoriatic / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002986:Clinical Trials as Topic; D016208:Databases, Factual; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D007155:Immunologic Factors / Q000009:adverse effects* / Q000627:therapeutic use; D007239:Infections / Q000453:epidemiology*; D009369:Neoplasms / Q000453:epidemiology / Q000401:mortality; D009894:Opportunistic Infections / Q000453:epidemiology; D011565:Psoriasis / Q000188:drug therapy; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D013167:Spondylitis, Ankylosing / Q000188:drug therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept